Purpose: Problem-based learning (PBL) is a well-established method for facilitating the learning of basic science concepts in the context of clinical cases. Relevant evidence is lacking regarding PBL’s effectiveness and acceptability as perceived by students accustomed to classical traditional teaching in India. Hence, this study gathered students’ opinions on PBL versus Traditional teaching methods to generate a foundation for institutional policymaking and ultimately, changes in the policy of regulatory bodies. Methods: A total of 773 first year medical students admitted from 2007-2010 in Kasturba Medical College Manipal, Manipal University, India were asked to respond to a 15-item questionnaire evaluating their preferences for PBL or traditional methods such as lectures after undergoing a systematically conducted PBL session in physiology. Their responses were analyzed with an unpaired t-test. Their comments were also collected. Results: PBL scored significantly higher for most items in the questionnaire for “learning efficiency” and “student-teacher relationship”. The students’ comments highlighted the importance of a trained tutor/facilitator to enhance the learning process. Conclusion: Our students are willing to adapt to the PBL method, although they recognize certain benefits of traditional pedagogy. For learning efficiency and the student-teacher relationship, the students feel that neither method holds an advantage. We recommend that the future medical curriculum in India be a hybrid form of PBL and traditional methods with specific training on the unfamiliar PBL approach for both faculty and students.